tbuckley/cabot-search huggingface dataset:
Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium
Authors: Bidisha Saha, Waheed Shabbir, Enzo Takagi, Xin-Peng Duan, Deise Carla Almeida Leite Dellova, John Demko, Anna Manis, Dominique Loffing-Cueni, Johannes Loffing, Mads Vaarby Sørensen, Wen-Hui Wang, David Pearce
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms. Background Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. Methods We used Cre-Lox–mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage. Results A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). Conclusions The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K + in vivo .
Alterations in the Circulating Proteome Associated with Albuminuria
Authors: Elizabeth Kiernan, Aditya Surapaneni, Linda Zhou, Pascal Schlosser, Keenan A. Walker, Eugene P. Rhee, Christie M. Ballantyne, Rajat Deo, Ruth F. Dubin, Peter Ganz, Josef Coresh, Morgan E. Grams
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. LMAN2, TNFSFR1B, and members of the ephrin superfamily had the strongest associations. Pathway analysis also demonstrated enrichment of ephrin family proteins. Background Proteomic techniques have facilitated understanding of pathways that mediate decline in GFR. Albuminuria is a key component of CKD diagnosis, staging, and prognosis but has been less studied than GFR. We sought to investigate circulating proteins associated with higher albuminuria. Methods We evaluated the cross-sectional associations of the blood proteome with albuminuria and longitudinally with doubling of albuminuria in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; mean GFR 46; median urine protein-to-creatinine ratio 81 mg/g; n =703) and replicated in two external cohorts: a subset of the Atherosclerosis Risk in Communities (ARIC) study with CKD and the Chronic Renal Insufficiency Cohort (CRIC). Results In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in AASK, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. Proteins with the strongest associations included LMAN2, TNFSFR1B, and members of the ephrin superfamily. Pathway analysis also demonstrated enrichment of ephrin family proteins. Five proteins were significantly associated with worsening albuminuria in AASK, including LMAN2 and EFNA4, which were replicated in ARIC and CRIC. Conclusions Among individuals with CKD, large-scale proteomic analysis identified known and novel proteins associated with albuminuria and suggested a role for ephrin signaling in albuminuria progression.
Author’s correction for Euro Surveill. 2023;28(9)
Journal: Eurosurveillance (2023)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Contaminated dicloxacillin capsules as the source of an NDM-5/OXA-48-producing Enterobacter hormaechei ST79 outbreak, Denmark and Iceland, 2022 and 2023
Multidrug-resistant Neisseria gonorrhoeae isolate SE690: mosaic penA-60.001 gene causing ceftriaxone resistance internationally has spread to the more antimicrobial-susceptible genomic lineage, Sweden, September 2022
Authors: Daniel Golparian, Nora Vestberg, Wiktor Södersten, Susanne Jacobsson, Makoto Ohnishi, Hong Fang, Karin Haij Bhattarai, Magnus Unemo
Journal: Eurosurveillance (2023)

We report a ceftriaxone-resistant, multidrug-resistant urogenital Neisseria gonorrhoeae in a female sex worker in Sweden, September 2022, who was treated with ceftriaxone 1 g, but did not return for test-of-cure. Whole genome sequencing of isolate SE690 identified MLST ST8130, NG-STAR CC1885 (new NG-STAR ST4859) and mosaic penA-60.001. The latter, causing ceftriaxone resistance in the internationally spreading FC428 clone, has now also spread to the more antimicrobial-susceptible genomic lineage B, showing that strains across the gonococcal phylogeny can develop ceftriaxone resistance.
A Novel Psychosocial Intervention for Motivational Negative Symptoms in Schizophrenia: Combined Motivational Interviewing and CBT
Authors: L. Felice Reddy, Shirley M. Glynn, Jessica E. McGovern, Catherine A. Sugar, Eric A. Reavis, Michael F. Green
Journal: American Journal of Psychiatry (2023)

Negative symptoms are a primary cause of disability in schizophrenia for which there are no established pharmacotherapies. This study evaluated a novel psychosocial intervention that combined two evidence-based practices-motivational interviewing and cognitive-behavioral therapy (MI-CBT)-for the treatment of motivational negative symptoms.Seventy-nine participants with schizophrenia and moderate to severe negative symptoms were included in a randomized controlled trial comparing the 12-session MI-CBT treatment with a mindfulness control condition. Participants were assessed at three time points through the study period, which included 12 weeks of active treatment and 12 weeks of follow-up. The primary outcome measures were motivational negative symptoms and community functioning; the secondary outcomes included a posited biomarker of negative symptoms: pupillometric response to cognitive effort.Compared with the control group, participants in the MI-CBT group showed significantly greater improvements in motivational negative symptoms over the acute treatment period. Their gains relative to baseline were maintained at follow-up, although the differential benefit relative to control subjects was attenuated. There were nonsignificant effects toward improvements in community functioning and differential change in the pupillometric markers of cognitive effort.The results show that combining motivational interviewing with CBT yields improvements in negative symptoms, a feature of schizophrenia generally thought of as resistant to intervention. Motivational negative symptoms not only responded to the novel treatment, but the gains were maintained over the follow-up period. Implications for future studies and for improving the generalization of the negative symptom gains to daily functioning domains are discussed.
Steroid Dose and Duration, Immortal Time Bias, and Survival After High-grade Immune-Related Adverse Events
Authors: Pankti Reid, Jeffrey A. Sparks, Anne R. Bass
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Sex-based epidemiological and immunovirological characteristics of people living with HIV in current follow-up at a tertiary hospital: a comparative retrospective study, Catalonia, Spain, 1982 to 2020
Authors: Sara Toyos, Leire Berrocal, Ana González-Cordón, Alexy Inciarte, Lorena de la Mora, María Martínez-Rebollar, Montserrat Laguno, Emma Fernández, Juan Ambrosioni, Iván Chivite, Elisa de Lazzari, José Luis Blanco, Esteban Martínez, José M Miró, Josep Mallolas, Berta Torres
Journal: Eurosurveillance (2023)

BackgroundEpidemiological and immunovirological features of people living with HIV (PLWH) can vary by sex.AimTo investigate, particularly according to sex, characteristics of PLWH who consulted a tertiary hospital in Barcelona, Spain, in 1982-2020.MethodsPLWH, still in active follow-up in 2020 were retrospectively analysed by sex, age at diagnosis, age at data extraction (December 2020), birth place, CD4+ cell counts, and virological failure.ResultsIn total, 5,377 PLWH (comprising 828 women; 15%) were included. HIV diagnoses in women appeared to decrease from the 1990s, representing 7.4% (61/828) of new diagnoses in 2015-2020. From 1997, proportions of new HIV diagnoses from patients born in Latin America seemed to increase; moreover, for women born outside of Spain, the median age at diagnosis appeared to become younger than for those born in Spain, with significant differences observed in 2005-2009 and 2010-2014 (31 vs 39 years (p = 0.001), and 32 vs 42 years (p < 0.001) respectively), but not in 2015-2020 (35 vs 42 years; p = 0.254). Among women, proportions of late diagnoses (CD4+ cells/mm3 < 350) were higher than men (significantly in 2015-2020: 62% (32/52) vs 46% (300/656); p = 0.030). Initially, virological failure rates were higher in women than men, but they were similar in 2015-2020 (12% (6/52) vs 8% (55/659); p = 0.431). Women ≥ 50 years old represented 68% (564/828) of women actively followed up in 2020.ConclusionsWomen still have higher rates of late HIV diagnoses than men. Among currently-followed-up women, ≥ 50 year-olds, who need age-adapted care represent a high percentage. Stratifying PLWH by sex matters for HIV prevention and control interventions.
Environmentally Adaptable Organo–Ionic Gel‐Based Electrodes for Real‐Time On‐Skin Electrocardiography Monitoring
Authors: Shuaimin Tang, Dongyong Sha, Zirui He, Xi Chen, Yifan Ma, Changsheng Liu, Yuan Yuan
Journal: Advanced Healthcare Materials (2023)

Abstract On‐skin personal electrocardiography (ECG) devices, which can monitor real‐time cardiac autonomic changes, have been widely applied to predict cardiac diseases and save lives. However, current interface electrodes fail to be unconditionally and universally applicable, often losing their efficiency and functionality under harsh atmospheric conditions (e.g., underwater, abnormal temperature, and humidity). Herein, an environmentally adaptable organo–ionic gel‐based electrode (OIGE) is developed with a facile one‐pot synthesis of highly conductive choline‐based ionic liquid ([DMAEA‐Q] [TFSI], I.L.) and monomers (2,2,2‐trifluoroethyl acrylate (TFEA) and N‐hydroxyethyl acrylamide (HEAA). In virtue of inherent conductivity, self‐responsive hydrophobic barriers, dual‐solvent effect, and multiple interfacial interactions, this OIGE features distinct sweat and water‐resistance, anti‐freezing and anti‐dehydration properties with strong adhesiveness and electrical stability under all kinds of circumstances. In contrast to the dysfunction of commercial gel electrodes (CGEs), this OIGE with stronger adhesion as well as skin tolerability can realize a real‐time and accurate collection of ECG signals under multiple extreme conditions, including aquatic environments (sweat and underwater), cryogenic (&lt;−20°C) and arid (dehydration) environments. Therefore, the OIGE shows great prospects in diagnosing cardiovascular diseases and paves new horizons for multi‐harsh environmental personalized healthcare.
Factors associated with disease-specific life impact in patients with hidradenitis suppurativa: results from the Global VOICE project
Authors: Amit Garg, Sahil Rawal, Oleg Akilov, Afsaneh Alavi, Christine Ardon, Falk G Bechara, Arnon D Cohen, Steven R Cohen, Steven Daveluy, Véronique del Marmol, Maïa Delage, Solveig Esmann, Shani Fisher, Evangelos J Giamarellos-Bourboulis, Amelia Glowaczewska, Noah Goldfarb, Elena Gonzalez Brant, Øystein Grimstad, Sandra Guilbault, Iltefat Hamzavi, Rosalind Hughes, John R Ingram, Gregor B E Jemec, Qiang Ju, Naomi Kappe, Brian Kirby, Joslyn S Kirby, Michelle A Lowes, Lukasz Matusiak, Stella Micha, Robert G Micheletti, Angela P Miller, Dagfinn Moseng, Haley B Naik, Aude Nassif, Georgios Nikolakis, So Yeon Paek, Jose Carlos Pascual, Errol Prens, Barry Resnik, Hassan Riad, Christopher Sayed, Saxon D Smith, Yssra Soliman, Jacek C Szepietowski, Jerry Tan, Linnea Thorlacius, Thrasyvoulos Tzellos, Hessel H van der Zee, Bente Villumsen, Lanqi Wang, Christos C Zouboulis, Andrew Strunk
Journal: British Journal of Dermatology (2023)

Patients with hidradenitis suppurativa experience significant life impact related to their disease. Younger age, Black race, high BMI, active smoking, flares, depression, anxiety, high comorbidity burden, disability, and difficult access to a dermatologist adversely influence life impact related to having hidradenitis suppurativa. Attention to these factors, particularly modifiable ones, may reduce overall impact of disease.
Evaluation of Health-Related Values and Preferences of Adults Who Were Preterm Infants and Parents of Preterm Infants Concerning Use of Prophylactic Cyclooxygenase Inhibitor Drugs
Authors: Souvik Mitra, Tara Hatfield, Marsha Campbell-Yeo, Jon Dorling, Bradley C. Johnston
Journal: JAMA Network Open (2023)

There is wide variability in the use of prophylactic cyclooxygenase inhibitor (COX-I) drugs to prevent morbidity and mortality in preterm infants. Parents of preterm infants are rarely involved in this decision-making process.To explore the health-related values and preferences of adults who were preterm infants and families of preterm infants concerning the prophylactic use of indomethacin, ibuprofen, and acetaminophen initiated within the first 24 hours after birth.This cross-sectional study used direct choice experiments conducted in 2 phases of virtual video-conferenced interviews between March 3, 2021, and February 10, 2022: (1) a pilot feasibility study and (2) a formal study of values and preferences, using a predefined convenience sample. Participants included adults born very preterm (gestational age <32 weeks) or parents of very preterm infants currently in the neonatal intensive care unit (NICU) or having graduated from the NICU in the last 5 years.Relative importance of clinical outcomes, willingness to use each of the COX-Is when presented as the only option, preference for using prophylactic hydrocortisone vs indomethacin, willingness to use any of the COX-Is when all 3 options are available, and relative importance of having family values and preferences included in decision-making.Of 44 participants enrolled, 40 were included in the formal study (31 parents and 9 adults born preterm). The median gestational age of the participant or the participant's child at birth was 26.0 (IQR, 25.0-28.8) weeks. Death (median score, 100 [IQR, 100-100]) and severe intraventricular hemorrhage (IVH) (median score, 90.0 [IQR, 80.0-100]) were rated as the 2 most critical outcomes. Based on direct choice experiments, most participants were willing to consider prophylactic indomethacin (36 [90.0%]) or ibuprofen (34 [85.0%]), but not acetaminophen (4 [10.0%]) when offered as the only option. Among participants who initially chose indomethacin (n = 36), if prophylactic hydrocortisone was offered as a potential therapy with the caveat that both cannot be used simultaneously, only 12 of 36 (33.3%) preferred to remain with indomethacin. Variability in preference was noted when all 3 COX-I options were available, indomethacin (19 [47.5%]) being the most preferred option followed by ibuprofen (16 [40.0%]), while the remainder opted for no prophylaxis (5 [12.5%]).The findings of this cross-sectional study of former preterm infants and parents of preterm infants suggest that there was minimal variability in how participants valued the main outcomes, with death and severe IVH being rated as the 2 most important undesirable outcomes. While indomethacin was the most preferred form of prophylaxis, variability was noted in the choice of COX-I interventions when participants were presented with the benefits and harms of each drug.
Voluntary Medical Male Circumcisions for HIV Prevention — 13 Countries in Eastern and Southern Africa, 2017–2021
Authors: Megan E. Peck, Katherine S. Ong, Todd Lucas, Pauline Harvey, Phenyo Lekone, Mpho Letebele, Vasavi T. Thomas, Vusi Maziya, Mandzisi Mkhontfo, Teruwork Gultie, Dejene Mulatu, Mesfin Shimelis, Tiruneh Zegeye, Ambrose W. Juma, Elijah Odoyo-June, Paul K. Musingila, John Njenga, Andrew Auld, Martin Kapito, Alice Maida, Wezi Msungama, Marcos Canda, Jotamo Come, Inacio Malimane, Mekondjo Aupokolo, Brigitte Zemburuka, Ida Kankindi, Samuel Malamba, Eric Remera, Emmanuel Tubane, Richard Machava, Nandi Maphothi, Peter Vranken, Mbaraka Amuri, Kokuhumbya J. Kazaura, Daimon Simbeye, Stella Alamo, Geoffrey Kabuye, Omega Chituwo, Royd Kamboyi, Joseph Masiye, John Mandisarisa, Sinokuthemba Xaba, Carlos Toledo
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In 2007, voluntary medical male circumcision (VMMC) was endorsed by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS after it was found to be associated with approximately a 60% reduction in the risk for female-to-male transmission of HIV (1). As a result of this endorsement, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), through partnerships with U.S. government agencies, including CDC, the U.S. Department of Defense, and the U.S. Agency for International Development, started supporting VMMCs performed in prioritized countries in southern and eastern Africa. During 2010-2016, CDC supported 5,880,372 VMMCs in 12 countries (2,3). During 2017-2021, CDC supported 8,497,297 VMMCs performed in 13 countries. In 2020, the number of VMMCs performed declined 31.8% compared with the number in 2019, primarily because of COVID-19-related disruptions to VMMC service delivery. PEPFAR 2017-2021 Monitoring, Evaluation, and Reporting data were used to provide an update and describe CDC's contribution to the scale-up of the VMMC program, which is important to meeting the 2025 Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 90% of males aged 15-59 years having access to VMMC services in prioritized countries to help end the AIDS epidemic by 2030 (4).
Risk of Experiencing an Overdose Event for Patients Undergoing Treatment With Medication for Opioid Use Disorder
Authors: Laura Brandt, Mei-Chen Hu, Ying Liu, Felipe Castillo, Gabriel J. Odom, Raymond R. Balise, Daniel J. Feaster, Edward V. Nunes, Sean X. Luo
Journal: American Journal of Psychiatry (2023)

Objective: Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD. Methods: Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models. Results: By week 24, 39 participants had ≥1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone. Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65). Conclusions: Among patients with opioid use disorder seeking medication treatment, the risk of overdose events over the next 24 weeks is elevated among those who fail to initiate or discontinue medication and those who report benzodiazepine use at baseline.